title: Compound K, a metabolite of ginseng saponin, inhibits colorectal cancer cell growth and induces apoptosis through inhibition of histone deacetylase activity.
abstract: In this study, we investigated the molecular mechanisms underlying the anti-proliferative effects of Compound K, with specific reference to histone modification. Exposure of HT-29 human colon cancer cells to Compound K resulted in time-dependent inhibition of histone deacetylase (HDAC) activity, mRNA and protein expression. Compound K treatment induced unmethylation of the RUNX3 promoter region such as TSA treatment and an accumulation of acetylated histones H3 and H4 within the total cellular chromatin, resulting in an enhanced ability of these histones to bind to the promoter sequences of the tumor suppressor gene Runt-related transcription factor 3 (RUNX3). Treatment of cells with Compound K increased the mRNA and protein expression of RUNX3, as well as p21, a downstream target of RUNX3. These alterations were consistent with cell cycle arrest at the G0/G1 phases and induction of apoptosis. Our results provide new insights into the mechanisms of Compound K action in human colorectal cancer cells and suggest that HDAC inhibition presents a novel approach to prevent or treat colorectal cancer.
authors.affiliation: School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 690-756, Republic of Korea.
authors.forename: Kyoung Ah
authors.initials: KA
authors.lastname: Kang
authors.forename: Mei Jing
authors.initials: MJ
authors.lastname: Piao
authors.forename: Ki Cheon
authors.initials: KC
authors.lastname: Kim
authors.forename: Jian
authors.initials: J
authors.lastname: Zheng
authors.forename: Cheng Wen
authors.initials: CW
authors.lastname: Yao
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Cha
authors.forename: Hye Sun
authors.initials: HS
authors.lastname: Kim
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Suk Chul
authors.initials: SC
authors.lastname: Bae
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Hyun
mesh_terms: D000107:Acetylation / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D036145:Ginsenosides / Q000494:pharmacology*; D019073:HT29 Cells; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000187:drug effects / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D005894:Panax; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D036145:Ginsenosides; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D006657:Histones; D006877:Hydroxamic Acids; D012333:RNA, Messenger; C493729:Runx3 protein, human; C012589:trichostatin A; C112772:ginsenoside compound K